Reliable diagnosis of a human disease, such as cancer, has the potential to alert health care providers to early onset of the disease. For many types of cancers, early detection can lead to early treatment, which, in turn, can significantly improve recovery and survival rates. Typically, cancer diagnosis relies on morphological examination of exfoliated or aspirated cells or surgically removed tissue samples. While considered as the “gold standard,” diagnosis based on morphological examination can be difficult and unreliable. In the case of metastatic adenocarcinoma, metastatic cancer cells and benign reactive mesothelial cells typically have similar morphological characteristics, thereby rendering differentiation between the two types of cells both time-consuming and prone to errors. Indeed, certain studies have shown that morphological examination alone (i.e., without any ancillary test) has an accuracy in the range of 50 percent to 70 percent with respect to diagnosing cancer in body cavity fluids. Due to this inaccuracy, various ancillary tests have been used in conjunction with morphological examination, such as histochemical, immunohistochemical, and ultrastructural tests. However, these ancillary tests themselves can be prone to errors with respect to diagnosing metastatic adenocarcinoma, and are typically considered as unsuitable for diagnosing other types of metastatic cancers, such as squamous cell carcinoma, melanoma, and sarcoma. Moreover, these ancillary tests often involve collection of relatively large quantities of samples that may not be readily available.
The past several years have seen considerable interest in identifying links between nanomechanical characteristics of cells and human diseases, and changes in nanomechanical characteristics of cells have recently emerged as a potential biomarker for diagnosis of human diseases. For example, the cytoskeleton is a subcellular structure of filaments and microtubules that provide a cell its shape, and the cytoskeleton influences both global and local nanomechanical characteristics of the cell. During malignant transformation, the cytoskeleton is dynamically altered or remodeled, which, in turn, can lead to changes in nanomechanical characteristics of the cell. Despite the progress that has been made, results of previous work remain lacking with respect to the goal of reliably diagnosing a disease state of living and substantially unmodified human cells, such as those that might be collected in a clinical setting. In particular, previous work has shown variability in nanomechanical characteristics among cells obtained from cell lines. However, because cell lines have been modified to render them immortal, results derived from cell lines typically cannot be readily extrapolated to predict results in an actual clinical setting for ex vivo human cells. In addition, previous work has shown a correlation in whole cell nanomechanical characteristics with respect to cancer cells and benign cells. However, because the observed correlation is slight, results indicate that whole cell or global measurements may not be sufficiently reliable for use in an actual clinical setting.
It is against this background that a need arose to develop the nanomechanical analysis and related systems and methods described herein.